Prolonged progression-free survival with zanubrutinib in relapsed/refractory CLL: an indirect treatment comparison versus other BTK inhibitors using multilevel network meta-regression.
Mazyar Shadman, Walter Bouwmeester, Leyla Mohseninejad et al.
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In 30 seconds
This multilevel network meta-regression compared zanubrutinib with acalabrutinib and ibrutinib for relapsed/refractory chronic lymphocytic leukemia, estimating effects in general and high-risk populations. It used individual patient data from the phase 3 ALPINE trial and aggregate data from ELEVATE-RR and ASCEND, all randomized trials. Zanubrutinib was associated with longer progression-free survival than ibrutinib (HR 0.67, 95% CrI 0.52-0.87) and acalabrutinib (HR 0.57, 95% CrI 0.34-0.95) in the general population; the PFS advantage was also seen in the high-risk population. Overall survival was similar but uncertain.
Key findings
- In general relapsed/refractory CLL, zanubrutinib improved PFS versus ibrutinib (HR = 0.67, 95% Credible Interval [CrI] = 0.52-0.87).
- Zanubrutinib improved PFS versus acalabrutinib in the general population (HR = 0.57, 95% CrI = 0.34-0.95).
- The PFS advantage over both comparators was maintained in the high-risk population with del(17p) and/or del(11q).
- OS was similar across BTK inhibitors in both populations, with wide credible intervals including no treatment difference.
Why it matters
PFS comparisons can inform understanding of relative BTK inhibitor outcomes when direct head-to-head evidence is unavailable for all treatments. The analysis suggests a PFS advantage for zanubrutinib across the modeled populations, while the uncertain OS findings mean that a survival benefit cannot be inferred from these results.
What to keep in mind
This is an indirect comparison combining individual patient data from one trial with aggregate data from two others; OS estimates were uncertain because of limited follow-up.